Infection with Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality worldwide, and causes serious disease in children and the elderly, including pneumonia, meningitis and bacteraemia, and some less severe infections such as otitis media. Almost one million children in the developing world die of infections due to pneumococcal disease each year.
The rapid emergence of multiple-drug-resistant strains of S. pneumoniae has limited the effectiveness of antibiotics and stimulated renewed interest in the prevention of pneumococcal infections with vaccines. Licensed pneumococcal vaccines consist of injectable polyvalent mixtures of serotype-specific capsular polysaccharides or capsular polysaccharide-protein conjugates and are therefore effective only against serotypes included. For example, although the 7-valent pneumococcal conjugate vaccine (PCV7) has significantly reduced the incidence of invasive pneumococcal disease due to vaccine-type (VT) strains, recent studies have shown that non-VT serotypes are gradually replacing VT serotypes, potentially limiting the usefulness of the vaccine. This has led to the evaluation of whether pneumococcal colonization can be prevented by immunization with serotype-independent antigens. For example, mucosal immunization with some proteins conserved widely throughout the S. pneumoniae species has been shown to elicit systemic and mucosal antibodies and to confer protection against pneumococcal disease and colonization.
Work continues to identify immunogenic compositions, including pneumococcal polysaccharides and proteins, that raise both antibodies and robust T lymphocyte-mediated immune responses to all serotypes. An alternative approach uses killed pneumococcal cells—which present multiple serotype-independent antigens—as an inexpensive vaccine, but the immunogenicity of these compositions has not been adequately explored previously. Hence, there remains a need for new approaches to the preparation of whole-cell pneumococcal vaccines, and an understanding of the mechanisms of immunity associated therewith.